Cystatin C: An improved detector of nephropathy in type 2 diabetic patients

ABSTRACT

The accurate estimation of glomerular filtration rate [GFR] appears to be important because diabetic nephropathy is the single most frequent cause of renal failure and nearly 40% of end stage renal disease patients receiving renal replacement therapy have diabetes mellitus, predominantly of type 2. The aim of this study was designed to assess the diagnostic accuracy of serum cystatin C, compared to the other traditional markers serum creatinine and Cockcroft and Gault estimated GFR [C and G formula], for the diagnosis of early diabetic nephropathy in patients with type 2 diabetes mellitus. The study was performed on 55 type 2 diabetic patients [25 males. 30 females] aged between 38 and 65 years. For all participants, renal function was assessed by measuring urinary albumin, serum creatinine, serum cystatin C using immunonephelometric assay, and by determining the inulin clearance [Cin] using the infusion Gin technique. We also calculated the C and G formula. Furthermore, levels of hemoglobin A1c glucose, serum lipids [total cholesterol, low-density lipoprotein cholesterol and triglycerides] were measured to assess risk factors for diabetic nephropathy. Results showed that cystatin C concentration progressively increased as GFR decreased. The overall relationship between the reciprocal cystatin C and GFR was significantly stronger [r=0.82] than those between serum creatinine and GFR [r=0.67] and between C and G formula and GFR [r=0.77]. As GFR decreased from 120 to 20 ml/min/1.73 m2, cystatin C increased more significantly than serum creatinine, giving a stronger signal in comparison to that of creatinine over the range of the measured GFR. The maximum diagnostic accuracy of serum cystatin C [88%] was significantly better than those of serum creatinine [73%] and C and G formula [82%] in discrimination between type 2 diabetic patients with normal GFR [>80 ml/min/1.73 m2] and those with reduced GFR [cystatin C cut-off limit of 0.98 mg/L corresponded to a false-positive rate of 7.5% and to a false-negative rate of 1.7%; the serum creatinine cut-off limit of 0.97 mg/dl corresponded to a false-positive rate of 5.6% and to a fasle-negative rate of 16.8%. Based on this study, serum cystatin C can be used as an alternative and more accurate marker than serum creatinine or the C and G formula in discriminating type 2 diabetic patients with a reduced GFR from those with a normal or near-to-normal GFR. Also, cystatin C is found to be a reliable marker that can confidentially be used in diagnosis of early diabetic nephropathy accompanied with mild impairment of GFR and allowing an earlier therapeutic treatment. Because our results show that cystatin C is superior for renal glomerular function assessment in a well-defined patient group, we recommend its measurement in the routine management of diabetic patients